Neuropeptide Y inhibits capsaicin-sensitive nociceptors via a Y1-receptor-mediated mechanism

J. Gibbs, C. M. Flores, K. M. Hargreaves

Research output: Contribution to journalArticlepeer-review


Neuropeptide Y (NPY) is expressed in certain primary afferent fibers, is up-regulated in response to tissue injury and is capable of inhibiting nociceptive behavior at the spinal level. However, the spinal mechanism(s) for NPY-evoked antinociception is unknown. In this study, we evaluated the hypothesis that agonists at the NPY Y1 receptor subtype (Y1-R) inhibit exocytosis from the capsaicin-sensitive class of nociceptors. Using in vitro superfusion of rat dorsal spinal cord slices, pre-treatment with the Y1-R agonist [Leu31Pro34]NPY significantly inhibited capsaicin-evoked release of immunoreactive calcitonin gene-related peptide with an EC50 value of 10.6 nM. This inhibitory effect was concentration dependent, significantly attenuated by pre-treatment with the Y1 receptor antagonist BIBP3226 and reproduced by synthetic NPY. Examination of adult rat dorsal root ganglia using double immunofluorescent labeling revealed frequent co-localization of Y1 receptor immunoreactivity in vanilloid receptor type 1-immunoreactive neurons, indicating that Y1 agonists may directly modulate the capsaicin-sensitive class of nociceptors. Collectively, these results indicate that NPY is capable of inhibiting capsaicin-sensitive neurons via a Y1 receptor mechanism, suggesting the mechanisms for spinal NPY-induced antinociception is due, at least in part, to inhibition of central terminals of capsaicin-sensitive nociceptors.

Original languageEnglish (US)
Pages (from-to)703-709
Number of pages7
Issue number3
StatePublished - 2004


  • Analysis of variance
  • CGRP
  • Calcitonin gene-related peptide
  • DRG
  • Dorsal root ganglion
  • Exocytosis
  • Immunoreactive calcitonin gene-related peptide
  • NGS
  • NPY
  • Neuropeptide Y
  • Normal goat serum
  • Pain
  • SP
  • Spinal cord
  • Superfusion
  • iCGRP

ASJC Scopus subject areas

  • General Neuroscience


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